Alkyl 6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylates

ABSTRACT

Lactones of the formula ##STR1## wherein R is hydrogen or a CX 3  group, and each X is a chlorine or bromine atom, are converted to the known cis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids or lower alkyl esters, from which pyrethroid insecticides are obtained.

This is a continuation in part of application Ser. No. 875,649, filedFeb. 6, 1978, now abandoned.

This invention relates to novel intermediates for the production ofcis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylates which arepyrethroid insecticides and to processes for making the intermediates.

Pyrethrins, naturally-occurring extracts of chrysanthemum flowers, havelong been of interest as insecticides. Certain man-made variations ofthe natural pyrethrins are much more potent than the natural materialsand exhibit other advantages. U.S. Pat. No. 4,024,163 discloses3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids,corresponding lower alkyl esters, and pyrethroid insecticides preparedfrom them. The acids and esters contain the following carboxylateradical, wherein X is chlorine or bromine. ##STR2## To producepyrethroid insecticides, the acids or the lower alkyl esters may beesterified (or transesterified) with various alcohols, e.g.,m-phenoxybenzyl alcohol, α-cyano-m-phenoxybenzyl alcohol, and otheralcohols well known to those skilled in the art.

These acids and esters are known to exist as both cis and transgeometrical isomers; the carboxy and dihalovinyl groups at C-1 and C-3may be either cis or trans with respect to each other. There aresubstantial differences in insecticidal activity between pyrethroidesters made from the cis and trans isomers of a givendihalovinylcyclopropanecarboxylic acid. In general, as between the cisand trans isomers of a given synthetic pyrethroid ester, the cis isomeris more active than the trans; the relative activities are reversed inthe natural esters.

C-1 and C-3 are assymetric, and the pyrethroid esters may be opticallyactive, their activity depending upon the stereoconfigurations at C-1and C-3. In general, the (1R,3R) isomers are the most active. Opticalisomers are named herein according to the "sequence rule" [see Cahn, etal., Angew. Chem., Intern. Ed. Engl., 5, 385 (1966)].

Because of the greater insecticidal activity of the cis esters,processes for producingcis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylates,essentially free of the trans isomers, are actively being sought.

Therefore, an object of this invention is to provide improved methodsfor producing both racemic and optically activecis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids andlower alkyl esters essentially free of the trans isomers. Another objectis the provision of novel intermediates for their production. Otherobjects will be apparent to those skilled in the art to which thisinvention pertains. Thecis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids andlower alkyl esters produced according to this invention may beesterified and converted into pyrethroid insecticides, with essentiallyno racemization or isomerization, according to methods disclosed in theprior art and well known to those skilled in the art. For example, theacid may be treated with thionyl chloride to produce the acid chloride,followed by reaction with an appropriate alcohol to produce aninsecticidal ester, and the lower alkyl ester may be transesterifiedwith an appropriate alcohol, both as disclosed in U.S. Pat. No.4,024,163 or in Elliott, et al., J. Agric. Food Chem., 24, 270 (1976),which disclosures are incorporated herein by reference.

This invention includes both process and composition embodiments. In oneprocess embodiment, this invention relates to a process for preparing alactone of the formula ##STR3## wherein R is hydrogen or a CX₃ group,and each X is a chlorine or bromine atom, which comprises cyclizing anoptically inactive diazo ester of the formula ##STR4## by intramolecularcarbenoid cyclization.

In other process aspects, this invention relates to processes for theproduction of novel intermediates, for example, malonic andalkanoylacetic esters of 3-methyl-2-buten-2-ol or a1,1,1-trihalo-4-methyl-3-penten-2-ol, as well as diazo derivatives ofthe esters, and 1-alkoxycarbonyl-substituted lactones, all useful asstarting materials for the production of lactones represented by theaforesaid formula.

In yet another process aspect, this invention relates to a process forpreparing, essentially free of the trans isomer, acis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid of theformula ##STR5## wherein the X's are the same or different, each X is achlorine or bromine atom, and the carboxy and dihalovinyl groups are ciswith respect to each other, which comprises subjecting to the Boordreaction, for example, treating with zinc and acetic acid, a compound ofthe formula ##STR6## wherein the X's are the same or different and havethe values given above, thereby simultaneously opening the lactone ringand eliminating one X atom.

In composition aspects, this invention relates to novel intermediatesuseful for the production ofcis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids andlower alkyl esters, from which pyrethroid insecticides may be preparedas described above.

The composition embodiments of the invention can be representedcollectively by structural formulae I, II and III below, wherein R is ahydrogen atom or a CX₃ group, the X's are the same or different, each Xis a chlorine or bromine atom, R¹ is lower alkyl or lower alkoxy, R² ishydrogen, lower alkoxycarbonyl, or lower alkanoyl, and R³ is hydrogen orlower alkoxycarbonyl. The term "lower" as used herein to modifyexpressions such as alkyl, alkoxy, etc., means a chain of 1-6,preferably 1-4 carbon atoms. ##STR7##

The composition embodiments of formula I are esters of alkanoylaceticand malonic acids, i.e., R¹ is lower alkyl or lower alkoxy,respectively. These novel esters may be prepared by esterifying3-methyl-2-buten-1-ol or 1,1,1-trihalo-4-methyl-3-penten-2-ols; forexample, with diketene or a lower alkylmalonyl chloride [see, e.g., U.S.Pat. No. 2,167,168, Kaneda, et al., Bull. Chem. Soc. Japan, 40, 228(1967), and Blomquist, J. Am. Chem. Soc., 70, 36 (1948)].

The composition embodiments of formula II, viz., the diazo derivativesof the aforesaid esters, and the lactones of formula III, can beproduced from the esters of formula I by process embodiments of thisinvention, as can the cis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids and lower alkyl esters--all as described hereinafter.

In preferred embodiments of this invention, the R² group is cleaved fromthe diazo derivatives of formula II, and the R³ group is cleaved fromthe lactones of formula III when R² is lower alkanoyl and R³ is loweralkoxycarbonyl, respectively, values arising when R¹ is lower alkyl andlower alkoxy, respectively, in the ester precursors of formula I. Itwill be apparent, therefore, that the exact nature of the R¹ group isnot critical. Therefore, contemplated equivalents of the compounds offormula I, and corresponding compounds of formulae II and III preparedfrom compounds of formula I by processes of this invention, are thosecompounds wherein R¹ is, e.g., alkyl or alkoxy of more than 6 carbonatoms, e.g, octyl and octyloxy; aryl and aryloxy, e.g., phenyl andphenoxy; aralkyl and aralkoxy, e.g., benzyl and benzyloxy, each of theforegoing bearing one or more simple substituents, e.g., halo, nitro,alkyl and alkoxy.

Processes and composition embodiments of this invention are exemplifiedin the following diagram. The invention is not to be construed aslimited to the specific embodiments which are illustrated. ##STR8##

In one process embodiment, an ester of formula I is subjected to a diazotransfer reaction, as described, for example, in Regitz, Synthesis, 351(1972), by reacting it with an azide, such as an arenesulfonyl azide,e.g., tosyl azide, or "polymer-bound" sulfonyl azide [see W. R. Roush,et al., Tetrahedron Letters, 1391 (1974)], to produce the correspondingdiazo compound of formula II.

When the ester of formula I is a 3-methyl-2-butenyl alkanoylacetate or a3-methyl-1-trihalomethyl-2-butenyl alkanoylacetate (R¹ is lower alkyl),a 3-methyl-2-butenyl or 3-methyl-1-trihalomethyl-2-butenyl2-diazoalkanoylacetate (formula II, R² is lower alkanoyl), respectively,is produced. Preferably, without isolation of this intermediate, thealkanoyl group is cleaved therefrom, e.g., with base, preferably aqueoussodium hydroxide, as described in Regitz, loc. cit., to yield directly a3-methyl-2-butenyl or 3-methyl-1-trihalomethyl-2-butenyl diazoacetate(formula II, R² is hydrogen), respectively. 3-Methyl-2-butenyl or a3-methyl-1-trihalomethyl-2-butenyl acetoacetate are especially preferredas the ester of formula I, since they may be prepared readily fromdiketene.

When the ester of formula I is a 3-methyl-2-butenyl or3-methyl-1-trihalomethyl-2-butenyl malonate (R¹ is lower alkoxy), it ispreferred that the ethyl ester be employed in the diazo transferreaction, producing an ethyl 3-methyl-2-butenyl or3-methyl-1-trihalomethyl-2-butenyl diazomalonate (formula II, R² isethoxycarbonyl).

It is preferable, however, to prepare a diazoacetate, rather than adiazomalonate, since the diazoacetate contains the hydrogen atomultimately desired at C-1 of thecis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid orester. Thus, it is preferred to use a 3-methyl-2-butenyl or3-methyl-1-trihalomethyl-2-butenyl alkanoylacetate (formula I, R¹ islower alkyl, e.g. methyl) as the starting material, and an acetoacetateis especially preferred.

A second process embodiment, also within the scope of this invention,for producing the preferred 3-methyl-2-butenyl or3-methyl-1-trihalomethyl-2-butenyl diazoacetate is to esterify3-methyl-2-buten-1-ol or a 1,1,1-trihalo-4-methyl-3-penten-2-ol with ahydrazone, e.g., the tosyl hydrazone, of glyoxoyl chloride.

In a third process embodiment, an optically inactive diazo derivative offormula II (compounds of formula II are chiral when R is CX₃), whereinR² is hydrogen or lower alkoxycarbonyl, which may be prepared asdescribed above, is cyclized, e.g., by intramolecular carbenoidcyclization, as disclosed, for example, in House, et al., J. Org. Chem.,33, 53 (1968), by treatment with a copper-containing catalyst, therebyyielding a bicyclic lactone, viz., a6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane or a4-trihalomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane of formulaIII, when R is H or CX₃, respectively. If the copper-containing catalystis not optically active, a racemic lactone is obtained, but thecyclization affords an optically active lactone when chiralcopper-containing catalysts, described below, are used. An unexpectedresult of using an achiral or racemic catalyst is that, whereas thereare two possible racemic pairs of the 4-trihalomethyl-substitutedlactone (4 optical isomers), only one racemic pair is produced, the(1R,4R,5S) optical isomer and its mirror image. Preferably, the startingcompound is a diazoacetate, thereby producing a compound of formula IIIwherein R³ is hydrogen.

Racemic mixtures or optically active enriched mixtures of the lactonesdescribed herein are resolved by methods known in the art, yielding theindividual optically active isomers; for example, Nozaki, et al.,Tetrahedron, 24, 3655 (1968) suggests opening the lactone ring,resolution of the acid, followed by lactonization.

It will be evident to those skilled in the art that other compoundscapable of generating the carbenoid intermediates so derived from theaforesaid diazo derivatives of formula II can also be employed toproduce bicyclic lactones of formula III.

Copper-containing catalysts which may be employed to produce racemiclactones include achiral or racemic coordination complexes of copper,e.g., cupric acetylacetonate, cupric salicylaldehydeiminate, cupricethylacetoacetate, as well as cuprous oxide, cupric oxide, cuprouschloride, cupric acetate, and metallic copper. Of these, achiral orracemic coordination complexes are preferred, and cupric acetylacetonateis especially preferred.

To effect cyclization to an optically active lactone, chiral binuclearcopper-containing catalysts selected from[N-(2-hydroxyethylate)salicylideneaminato]copper(II) binuclear complexesare employed. Examples of these catalysts include optically activebis[2-butoxy-α-(2-butoxy-5-methylphenyl)-α-[1-[[(2-hydroxyphenyl)methylene]amino]ethyl]-5-methylbenzenemethanolato(2-)]-copperandbis[2-butoxy-α-[2-butoxy-5-(1,1-dimethylethyl)phenyl]-5-(1,1-dimethylethyl)-α-[1-[[2-hydroxyphenyl)methylene]amino]ethyl]benzenemethanolato(2-)]-copper.Catalysts of (S) stereochemistry, e.g.,bis[2-butoxy-5-methylphenyl)-α-[(S)-1-[[(2-hydroxyphenyl)methylene]amino]ethyl]-5-methylbenzenemethanolato(2-)]-copperandbis[2-butoxy-α-[2-butoxy-5-(1,1-dimethylethyl)phenyl]-5-(1,1-dimethylethyl)-α-[(S)-1-[[2-hydroxyphenyl)methylene]amino]ethyl]benzenemethanolato(2-)]-copper,are preferred because they afford optically active lactones which may becarried, by processes described below, tocis-3-(2,2-dihalovinyl)2,2-dimethylcyclopropanecarboxylic acids oresters, which are optically active due to enrichment with the (1R,3R)isomers. Among these catalysts, bis[2-butoxy-α-[2-butoxy-5-(1,1-dimethylethyl)phenyl]-5-(1,1-dimethylethyl)-α-[(S)-1-[[2-hydroxyphenyl)methylene]amino]ethyl]benzenemethanolato(2-)]-copperis especially preferred. Catalysts of (R) stereochemistry give riseultimately to acids or esters which are rich in the (1S,3S) enantiomers.The catalysts may be prepared from optically active ethyl alanine bycoupling with a Grignard reagent, producing a salicylaldimine from theresultant amino alcohol, and treating the imine with cupric acetate, allaccording to the method disclosed by Aratini, et al. in TetrahedronLetters, 1707 (1975), which disclosure is incorporated herein byreference.

Aprotic solvents may be employed in the cyclization, e.g., aromatichydrocarbons and ethers, preferably toluene, benzene, n-octane,cyclohexane, or dioxane. In general, dioxane is preferred, but tolueneis preferred for the tribromomethyl compounds. Improved yields areobtained if the reaction is conducted at high dilution.

In a fourth process embodiment, a bicyclic lactone of formula III,wherein R³ is a lower alkoxycarbonyl group, preferably methoxycarbonyl,is subjected to dealkoxycarbonylation, e.g., by treatment with lithiumchloride in a polar solvent selected from hexamethylphosphoric triamide,dimethylformamide and dimethylsulfoxide, or mixtures thereof with water,cleaving the lower alkoxycarbonyl group and producing the correspondinglactone of formula III wherein R³ is hydrogen. A starting lactoneproduced as described above using a chiral catalyst of (S)stereochemistry affords a cleaved optically active lactone which can becarried, as described below, tocis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids oresters, which are optically active due to enrichment with the (1R,3R)isomers.

In a fifth process embodiment, a bicyclic lactone of formula III,wherein R is hydrogen, is converted into a lower alkylcis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylate. Forexample, Sevrin, et al., Tetr. Letters, 3915 (1976) describe thetreatment of 6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane with base toopen the ring, followed by acidification and methylation withdiazomethane, producing methylcis-3-hydroxymethyl-2,2-dimethylcyclopropanecarboxylate. The alcohol isthen oxidized to methylcis-3-formyl-2,2-dimethylcyclopropanecarboxylate. Japan. Kokai 76/122041discloses the addition of a tri- or tetrahalomethane to the methyl3-formyl-2,2-dimethylcyclopropanecarboxylate, followed by acylation ofthe resulting 3-(1-hydroxy-1-trihalomethyl)derivative and reduction ofthe acylated compound with metallic zinc to afford a methyl3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylate. It is preferredto employ the lactone wherein R³ is hydrogen, since6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane yields directly a loweralkyl cis ester which may be converted into a pyrethroid insecticide bymethods well known in the art and referred to above, i.e., U.S. Pat. No.4,034,163. In the case that R³ is lower alkoxycarbonyl, the resultant1-alkoxycarbonylcyclopropanecarboxylate may be dealkoxycarbonylated,e.g., as disclosed in U.S. Pat. No. 4,000,180, and then converted into apyrethroid insecticide. Further, if an optically active lactone isemployed, it is not only preferred that it be6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane, but that the opticalactivity be due to enrichment with the (1R,5S) isomer, since anoptically active cyclopropanecarboxylic enriched with the (1R,3R) isomeris then obtained. Optically active6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane which is rich in the(1R,5S) isomer is obtained, e.g., by the process embodiments describedabove, provided that the diazo ester is cyclized with a chiral binuclearcopper-containing catalyst having (S) stereochemistry.

In a sixth process embodiment, a bicyclic lactone of the formula III,wherein R is CX₃, is subjected to the elimination reaction known as theBoord reaction, described, e.g., in J. March, "Advanced OrganicChemistry: Reactions, Mechanisms, and Structure," McGraw-Hill Book Co.,Inc., New York, N.Y., 1968, p. 771, by treatment with a metal selectedfrom zinc, magnesium, sodium, or coordination complexes of Cr(II), in asolvent selected from acetic acid, alcohols such as ethanol, and ethers,such as tetrahydrofuran and diethyl ether, and mixtures thereof, therebysimultaneously opening the lactone ring, eliminating one halogen atom,and producing essentially free of the trans isomer, acis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid, i.e.,wherein the carboxy and dihalovinyl groups are cis with respect to eachother. Preferably, the metal is zinc and the solvent is a mixture of anether and acetic acid. It is preferred that R³ by hydrogen, since thecyclopropanecarboxylic acid may then be converted directly into apyrethroid insecticide as described above, e.g., see U.S. Pat. No.4,034,163. In the case that R³ is lower alkoxycarbonyl, the resultant1-alkoxycarbonylcyclopanecarboxylic acid may be dealkoxycarbonylated,e.g., via the esters as disclosed in U.S. Pat. No. 4,000,180, and thenconverted into a pyrethroid insecticide. Further, if an optically activelactone is employed, it is not only preferred that it be a4-trihalomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane, but thatthe optical activity be due to enrichment with the (1R,4R,5S) isomer,since an optically active cyclopropanecarboxylic acid enriched with the(1R,3R) isomer is then obtained. An optically active4-trihalomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane which isrich in the (1R,4R,5S) isomer is obtained, e.g., by the processembodiments described above, provided that the diazo ester is cyclizedwith a chiral binuclear copper-containing catalyst having (S)stereochemistry.

Since the Boord reaction involves the elimination of only one halogenatom from the trihalomethyl group at C-4 of a4-trihalomethyl-substituted lactone of formula III, and since thetrihalomethyl group is not a reactive center in the processes leading tothe lactone, it will be apparent that two of the halogen atoms in thecompounds of formulae I, II, or III can be replaced by othersubstituents in any of the processes of this invention, e.g., two of thehalogen atoms can be independently hydrogen; halogen; cyano; lower alkylof 1 to 4 carbon atoms, which may be substituted with one or morehalogen atoms; and ##STR9## where Y is --CH₂ --, --O--, --S--, orabsent, and the phenyl group may be substituted with one or morehalogen, lower alkyl (1 to 4 carbon atoms), lower haloalkyl, loweralkoxy, or lower alkylthio groups. In addition, it will be evident tothose skilled in the art that various derivatives of acis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid, ratherthan the acid itself, can be obtained from the Boord reaction by varyingthe manner in which the lactone of formula III is opened; e.g., when thelactone is treated with methanolic potassium carbonate followed by zincand acetic acid, a methyl dihalovinylcyclopropanecarboxylate isobtained.

In a preferred multistep process embodiment, acis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid isproduced by treating a (±)-3-methyl-1-trihalomethyl-2-butenylacetoacetate of formula I with tosyl azide to effect diazo transfer,followed by sodium hydroxide to cleave the acetyl group and produce a(±)-3-methyl-1-trihalomethyl-2-butenyl diazoacetate of formula II, whichin turn is subjected to intramolecular carbenoid cyclization with cupricacetylacetonate to produce a4-trihalomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane of formulaIII, which is then treated in the Boord reaction with zinc and aceticacid to produce acis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid.

Although any compound of formulae I, II, and III wherein R is a CX₃group may contain both chlorine and bromine and may be employed in theaforesaid processes, the trichloro and tribromo compounds are preferred,and the yields are generally higher with the chlorine-containingcompounds. Thus, the processes disclosed above are especially wellsuited to preparing acis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid orlower alkyl ester. The dibromovinyl acids or esters may be prepared inexcellent yield by exchanging the halogen in the dichlorovinyl acid or alower alkyl ester thereof as disclosed in the application of Kondo andMatsui, entitled "Process for Converting 2,2-Dichlorovinylcyclopropanesto Dibromovinyl Analogs," filed concurrently with application Ser. No.875,649, parent to the instant application.

The invention will be understood more completely by reference to thefollowing preparative examples.

In the Examples which follow, temperatures are in degrees Celsius andpressures are in mm Hg. Tetramethylsilane was employed as an internalstandard for the nmr spectra. In reporting the nmr data theabbreviations have the following significance: s, singlet; d, doublet;t, triplet; q, quartet; m, multiplet. Any of the abbreviations may beproceded by b for broad or d for double, for example, d.d., doubledoublet; b.t., broad triplet.

EXAMPLE I Synthesis of4-Trihalomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexanes A. From3-methyl-1-trihalomethyl-2-butenyl diazoacetates 1. Preparation of1,1,1-trichloro-4-methyl-3-penten-2-ol

To a solution of isobutene (89 g, 1.6 moles) and chloral (80 g, 0.52mole) in about 100 ml of petroleum ether (bp, 30°-70°), maintained at-5° to -10°, was added portionwise over a period of 30-60 minutes 6.08 gof anhydrous aluminum trichloride. The solution was stirred vigorouslyduring the addition and thereafter for five hours at -5° to -10°, thenovernight at room temperature.

After diluting the solution with ether, it was washed with 50-100 ml ofwater, dried over magnesium sulfate and distilled. After distillation ofthe petroleum ether, 1,1,1-trichloro-4-methyl-4-penten-2-ol (74.9 g, 71%yield)) was obtained; bp, 106°-118°/25 mm.

1,1,1-Trichloro-4-methyl-4-penten-2-ol (74 g, 0.36 mole) was heated at140°-150° for 18 hours. After cooling, the alcohol was diluted withether, and the ethereal solution was treated with activated charcoal.The ether was removed by evaporation to afford crystalline1,1,1-trichloro-4-methyl-3-penten-2-ol (43.4 g, 59% yield) afterrecrystallization from petroleum ether.

1,1,1-Tribromo-4-methyl-3-penten-2-ol is similarly prepared bysubstituting bromal for chloral in the reaction.

2. Preparation of 3-methyl-1-trichloromethyl-2-butenyl acetoacetate

A mixture of 1,1,1-trichloro-4-methyl-3-penten-2-ol (20.4 g, 0.1 mole)and anhydrous sodium acetate (0.04 g) were heated together at 90°-95°until the trichloro alcohol melted. Diketene (13.2 ml, 0.11 mole) wasadded dropwise in one hour to the mixture maintained at 80°-83°. Themixture was then maintained at 80°-83° for an additional two hours.

The reaction mixture was diluted with ether, and the ethereal solutionwas washed successively with aqueous 1N hydrochloric acid, saturatedaqueous sodium bicarbonate, and saturated aqueous sodium chloride. Thesolution was then dried over magnesium sulfate, and the ether wasevaporated, leaving a residue which was distilled under vacuum,affording 3-methyl-1-trichloromethyl-2-butenyl acetoacetate (25.3 g, 88%yield); bp, 95°-96°/0.23 mm.

3. Preparation of 3-methyl-1-tribromomethyl-2-butenyl acetoacetate

1,1,1-Tribromo-4-methyl-3-penten-2-ol (6.72 g, 0.02 mole) and anhydroussodium acetate (0.008 g) were melted together at 90°. The temperature ofthe mixture was then reduced to 80°, and diketene (about 2.6 ml, 0.022mole) was added dropwise over a 10 minute period. The resulting mixturewas heated at 80° for three additional hours. After cooling, the mixturewas diluted with ether, and the ethereal solution was washed with 1Naqueous hydrochloric acid and then ten times with saturated aqueoussodium bicarbonate. The washed mixture was treated with activatedcharcoal and dried over magnesium sulfate. Evaporation of the etherafforded 3-methyl-1-tribromomethyl-2-butenyl acetoacetate (8.34 g, 99%yield) as an oily residue.

Analysis: nmr δ ppm: 6.02(d, 1H); 5.25(m, 1H); 3.53(s, 2H); 2.32(s, 3H);1.85(m, 6H).

4. Preparation of 3-methyl-1-trichloromethyl-2-butenyl diazoacetate from3-methyl-1-trichloromethyl-2-butenyl acetoacetate

To a solution of 3-methyl-1-trichloromethyl-2-butenyl acetoacetate (5.75g, 0.02 mole) and triethylamine (2.02 g, 0.02 mole) in 50 ml ofacetonitrile was added a solution of tosyl azide (3.94 g, 0.02 mole,prepared according to the method of Organic Synthesis Collective VolumeV, page 179A) in acetonitrile dropwise over a period of 10 minutes. Theresultant mixture, containing the thus produced3-methyl-1-trichloromethyl-2-butenyl-2-diazoacetoacetate, was stirred atroom temperature for two hours and then poured into 60 ml (0.06 mole) of1N aqueous sodium hydroxide. The resulting mixture was stirred at roomtemperature for 30 minutes and then extracted with about 100 ml ofether. After phase separation, the aqueous layer was extracted with anadditional 150 ml portion of ether, and the ether extracts werecombined. The ethereal solution was then washed ten times with 50 mlportions of 3% aqueous potassium hydroxide containing sodium chlorideand then three times with 50 ml portions of saturated aqueous sodiumchloride. The washed ethereal solution was dried over magnesium sulfate,and the ether was removed by evaporation, affording a brown oilyresidue. The residue was purified by column chromatography on silica gelusing benzene as the eluent, to give3-methyl-1-trichloromethyl-2-butenyl diazoacetate (4.63 g, 85% yield).

5. Preparation of 3-methyl-1-tribromomethyl-2-butenyl diazoacetate

To a solution of 3-methyl-1-tribromomethyl-2-butenyl acetoacetate (8.32g, 0.0198 mole) and tosyl azide (3.9 g, 0.0198 mole) in 40 ml ofacetonitrile was added dropwise over a period of 35 minutes a solutionof triethylamine (2.0 g, 0.020 mole) in 10 ml of acetonitrile. Theresulting mixture was stirred at room temperature for 21/2 hours to give3-methyl-1-tribromomethyl-2-butenyl diazoacetoacetate. Then 60 ml of 1Naqueous sodium hydroxide was added thereto, and the mixture was stirredat room temperature for 45 minutes. The reaction mixture was thendiluted with ether, the organic phase was separated, the aqueous phasewas extracted with ether, and the organic phases were combined. Theethereal solution was washed with three successive portions of 3%aqueous potassium hydroxide containing sodium chloride, then three timeswith saturated aqueous sodium chloride. The washed ethereal solution wasdried over magnesium sulfate and treated with active charcoal.Evaporation of the ether afforded an oily residue. 3-Methyl-1-tribromomethyl-2-butenyl diazoacetate (5.78 g, 71% yield) was isolatedtherefrom by column chromatography.

Analysis: nmr δ ppm (CDCl₃): 1.85(dd, 6H); 4.82(s, 1H); 5.33(dq, 1H);6.03(d, 1H).

6. Preparation of 3-methyl-1-trichloromethyl-2-butenyl diazoacetate fromthe tosyl hydrazone of glyoxyloyl chloride

To a cold (0°) solution of the tosyl hydrazone of glyoxyloyl chloride(2.61 g, 0.01 mole, prepared according to the method of OrganicSynthesis Collective Volume V, page 259), and1,1,1-trichloro-4-methyl-3-penten-2-ol (2.035 g, 0.01 mole) in 25 ml ofmethylene chloride was added dropwise over a period of 20 minutes asolution of triethylamine (2.02 g, 0.02 mole) in 8 ml of methylenechloride. After stirring for one hour at 0°, the methylene chloride wasevaporated at 25° under vacuum, leaving a residue. The residue wasdissolved in 50 ml of benzene, and the dark brown solution was treatedwith activated charcoal and evaporated to give a yellow-brown oil. Theoil was dissolved in methylene chloride, and the solution was washedsuccessively twice with cold water, twice with cold aqueous sodiumbicarbonate, and twice with cold water. The solution in methylenechloride was dried over sodium sulfate and evaporated at 25° undervacuum to give methyl-1-trichloromethyl-2-butenyl diazoacetate (2.67 g,99% yield of crude product) as a viscous oil.

Analysis: ir (cm⁻¹): 2970, 2950, 2900, 2130, 1770, 1740, 1700, 1440,1340, 1310, 1270, 1200, 1170, 1095, 1070, 970, 840, 830, 800, 770, 750,630, 560, 540, 450.

3-Methyl-1-trichloromethyl-2-butenyl diazoacetate, prepared similarly,except that the triethylamine was added in two portions an hour apart,the resulting mixture was then stirred for 2.5 hours at 0°, and theproduct was purified by column chromatography, displayed the followingnmr spectrum.

nmr δ ppm (CCl₄): 5.93(d, 1H); 5.23(dq,1H); 4.72(s, 1H); 1.87(t, 6H).

7. Preparation of(±)-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane

To a refluxing solution of cupric acetylacetonate (0.07 g, 0.27 mole) in70 ml of dioxane was added dropdropwise over a 31/2 hour period, underan argon atmosphere, a solution of(±)-3-methyl-1-trichloromethyl-2-butenyl diazoacetate (1.09 g, 0.004moles) and cupric acetylacetonate (0.007 g, 0.027 mmole) in 10 ml ofdioxane. The reaction mixture was then heated under reflux for one hourand evaporated to dryness, yielding a residue which was dissolved inether. The ethereal solution was washed successively with two portionsof aqueous 1N hydrochloric acid, two portions of aqueous sodiumbicarbonate, and twice with saturated aqueous sodium chloride. Afterdrying the solution over magnesium sulfate, the ether was evaporated toafford a pale yellow oil, which was purified by column chromatograpy ona silica gel column using a 9/1 mixture of n-hexane/ethyl acetate as theeluent, to give(±)-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane (0.55g, 53% yield).

8. Preparation of optically active4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane

A solution of (±)-3-methyl-1-trichloromethyl-2-butenyl diazoacetate(0.544 g, 2 mmole) in dioxane (5 ml) was added dropwise over a period ofabout 4.5 hours to a suspension ofbis-[2-butoxy-α-[2-butoxy-5-(1,1-dimethylethyl)phenyl]-5-(1,1-dimethylethyl)-α-[(S)-1-[[(2-hydroxyphenyl)methylene]amino]ethyl]benzenemethanolato-(2-)]copper (0.762 g, 0.05 mmole) in dioxane (35 ml) at 100°-105°. When theevolution of nitrogen began, the temperature was slowly lowered to 50°and maintained at 50° throughout the addition. After the addition of the3-methyl-1-trichloromethyl-2-butenyl diazoacetate was completed, thereaction mixture was stirred at 50° for 2 hours. The reaction mixturewas then evaporated to dryness under vacuum and the residue dissolved indiethyl ether. The ethereal solution was washed with a 1N aqueoussolution of hydrochloric acid until the washings did not turn blue whentested with aqueous ammonia, then washed once with a saturated aqueoussolution of sodium chloride and dried over magnesium sulfate. The etherwas evaporated under vacuum, and the crude4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane enrichedwith the (1R,4R,5S) isomer (0.47 g) was converted by zinc reduction to3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid. The acid,after purification by column chromotagraphy, had an optical rotation of[α]_(D) ¹⁸.5 =+4.7° (CHCl₃). The optical yield of(1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acidfrom the (±)-3-methyl-1-trichloromethyl-2-butenyl diazoacetate wascalculated to be about 14%.

Optically active4-tribromomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane enrichedwith the (1R,4R,5S) isomer is similarly prepared from(±)-3-methyl-1-tribromomethyl-2-butenyl diazoacetate.

Optically active lactones enriched with the (1S,4S,5R) isomers areprepared by substituting the (R) catalyst for the (S) catalyst specifiedabove.

9. Preparation of(±)-4-tribromomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane

To a refluxing solution of cupric acetylacetonate (0.005 g, 0.019 mmole)in 40 ml of toluene was added dropwise over a period of 2.5 hours underan atmosphere of argon gas a solution of(±)-3-methyl-1-tribromomethyl-2-butenyl diazoacetate (0.203 g, 0.005 ml)in 10 ml of toluene. The mixture was then heated under reflux for onehour. After cooling, the reaction mixture was washed successively withtwo portions of 1N aqueous hydrochloric acid, once with saturatedaqueous sodium bicarbonate, and twice with saturated aqueous sodiumchloride. After drying over magnesium sulfate, the solution wasevaporated to give a yellow oil as the residue. The residue was purifiedby column chromatography on a silica gel column using 9/1 n-hexane/ethylacetate as the eluent, yielding(±)-4-tribromomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane (0.053g, yield 28%); mp 101°-103° after recrystallization from n-hexane.

Analysis: Calculated for C₈ H₉ Br₃ O₂ : C,25.50; H,2.41; Found: C,25.52;H,2.36.

nmr δ ppm (CDCl₃): 1.28(2s, 6H); 2.18 (d, 1H). 2.37(d, 1H); 4.58 (s,1H).

The nmr spectrum indicates that the lactone is the (1S,4S,5R)/(1R,4R,5S) racemic mixture.

10. Preparation of1-trichloromethyl-3-methyl-2-butenyl-2-diazoacetoacetate

To a solution of 1-trichloromethyl-3-methyl-2-butenyl acetoacetate(0.575 g, 2 mmole) and triethylamine (0.404 g, 4 mmole) in 10 ml ofacetonitrile was added 1 g of polymer-bound sulfonyl azide (prepared bythe method of Roush, et al., loc. cit.). The mixture was stirredovernight at room temperature and filtered. The filter cake was washedwith ether, and the slurry was filtered. Solvent was removed byevaporation from the combined filtrates to give1-trichloromethyl-3-methyl-2-butenyl 2-diazoacetoacetate (0.60 g, 96%yield).

Analysis: nmr δ ppm: 6.03 (d, 1H); 5.28 (bd, 1H); 2.45 (s, 3H); 1.90 (d,6H).

B. From lower alkyl 3-methyl-1-trichloromethyl-2-butenyldiazomalonates 1. Preparation of ethyl3-methyl-1-trichloromethyl-2-butenyl malonate

To a solution of 1,1,1-trichloro-4-methyl-3-penten-2-ol (7.98 g, 0.0392mole) and pyridine (3.10 g, 0.0392 mole) in 8 ml of ether was addeddropwise a solution of ethyl malonyl chloride (5.87 g, 0.039 mole) in 4ml of ether. The reaction mixture was then stirred overnight at roomtemperature.

The reaction mixture was diluted with ether and then washed with aqueous1N hydrochloric acid, then aqueous sodium bicarbonate, followed byaqueous medium chloride. The washed mixture was dried over magnesiumsulfate, the ether was removed by evaporation, and the residue wasdistilled to afford ethyl 3-methyl-1-trichloromethyl-2-butenyl malonate(5.68 g, 46% yield); bp, 104°-105°/0.3 mm.

Analysis: nmr δ ppm: 6.00(d, 1H); 5.32(dq, 1H); 4.18(dd, 2H); 3.35(s,2H); 1.88(m, 6H); 1.30(t, 3H).

2. Preparation of ethyl 3-methyl-1-trichloromethyl-2-butenyldiazomalonate

To a solution of ethyl 3-methyl-1-trichloro-methyl-2-butenyl malonate(5.63 g, 0.0177 mole) and triethylamine (1.79 g, 0.0177 mole) in 40 mlof acetonitrile was added dropwise a solution of tosyl azide (3.487 g,0.0177 mole) in 10 ml of acetonitrile. After the addition, the mixturewas stirred overnight at room temperature.

The acetonitrile was then evaporated from the solution at roomtemperature under vacuum, yielding a residue, which was dissolved inether. The ethereal solution was washed successively with three portionsof 3% aqueous potassium hydroxide and once with aqueous sodium chloride.After drying the solution over magnesium sulfate, the ether wasevaporated to yield ethyl 3-methyl-1-trichloromethyl-2-butenyldiazomalonate (5.91 g, 85% yield) as the residue.

Analysis: nmr δ ppm (CCl₄): 6.03(d, 1H); 5.30(dq, 1H); 4.27(dd, 2H);1.88(m, 6H); 1.33(t, 3H).

3. Preparation of ethyl(±)-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate

To a refluxing suspension of copper powder (5.0 g, 0.079 mole) in 240 mlof n-octane was added dropwise in one hour a solution of ethyl(±)-3-methyl-1-trichloromethyl-2-butenyl diazomalonate (5.0 g, 0.0146mole) in 60 ml of n-octane. The reaction mixture was then heated underreflux for 21/2 hours and filtered. The n-octane was removed from thefiltrate by evaporation under vacuum, yielding a residue which wasdistilled under vacuum to give ethyl(±)-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo-[3.1.0]hexane-1-carboxylateas a highly viscous oil (2.47 g, 54% yield); bp, 123°-125°/0.3 mm.

Analysis: nmr δ ppm (CCl₄): 4.47(s, 1H); 4.23(dd, 2H); 2.67(s, 1H);1.32(m, 9H).

4. Preparation of methyl(±)-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate

To a refluxing suspension of copper powder (6.6 g, 0.104 mole) in 320 mlof n-octane was added dropwise in one hour a solution of methyl(±)-3-methyl-1-trichloromethyl-2-butenyl diazomalonate (6.6 g, 0.02mole, prepared as described above for the ethyl ester) in 80 ml ofn-octane. The reaction mixture was heated for 21/2 hours under refluxand then filtered while hot. The n-octane was evaporated from thefiltrate under vacuum to produce a residue which was dissolved in ethylacetate. The solution was washed successively with aqueous 1Nhydrochloric acid, aqueous sodium bicarbonate, and aqueous sodiumchloride. After drying the solution over magnesium sulfate, the ethylacetate was removed by evaporation, yielding methyl(±)-4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate(5.77 g, 96% yield) as an oil. Trituration of the oil with etherafforded the crystalline lactone; mp, 118°-120°.

Analysis: Calculated for C₁₀ H₁₁ O₄ Cl₃ : C, 39.83; H, 3.68; Found: C,39.57; H, 3.56.

nmr δ ppm (CDCl₃): 4.39(s,1H); 3.76 (s,3H); 2.61(s,1H); 1.30 (s, 6H).

mass spec. m/e: 300, 109, 100, 33, 18. molecular weight (CHCl₃): 295

The nmr spectrum indicates that the lactone is the (1S,4S,5R)/(1R,4R,5S) racemic mixture.

5. Preparation of4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane

To a solution of methyl4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate(1.52 g, 0.005 mole) in 10 ml of hexamethylphosphoric triamide was addedlithium chloride (0.42 g, 0.010 mole). After heating at 75° for twohours, the cooled reaction mixture was diluted with ether. The etherealsolution was washed with water, dried over magnesium sulfate, and theether was removed by evaporation, yielding a residue which was purifiedby column chromatography on silica gel using 9/1 n-hexane/ethylacetateas the eluent to give4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane (0.34 g,28% yield) as an oil.

Analysis: nmr δ ppm (CDCl₃): 4.60(s, 1H); 2.37(d, 1H); 2.15(d, 1H);1.28(s, 6H).

mass spec. m/e: 243, 125, 100, 97, 30.

Following the above procedure, the same compound is prepared from ethyl4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate.

EXAMPLE II Synthesis of 6,6-Dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane 1.Preparation of 3-methyl-2-butenyl acetoacetate

A mixture of 3-methyl-2-buten-1-ol (21.2 g, 0.25 mole) and anhydroussodium acetate (0.1 g) was cooled to 0°. Diketene (36 ml, 0.3 mole) wasadded dropwise over a period of 1.5 to 2 hours. The reaction mixture wasthen heated to 75°-80°, and this temperature was maintained for onehour. The mixture was diluted with ether. The ethereal solution waswashed successively with aqueous 1N hydrochloric acid, saturated aqueoussodium bicarbonate, saturated aqueous sodium chloride, and then driedover magnesium sulfate. The ether was evaporated, leaving a residuewhich was distilled under vacuum, affording 3-methyl-2-butenylacetoacetate (32.1 g, 76% yield); bp 114°-117°/18-19 mm.

2. Preparation of 3-methyl-2-butenyl diazoacetate

A solution of 3-methyl-2-butenyl acetoacetate (7.4 g, 0.0435 mole) andp-toluenesulfonyl azide was prepared in acetonitrile. Triethylamine(4.40 g) in acetonitrile was added dropwise to this solution over aperiod of 10 minutes, and the stirred reaction mixture was maintained atroom temperature for 2 hours. An aqueous 1N solution of sodium hydroxide(130 ml, 0.13 mole) was added and stirring continued for 45 minutes.Ether and aqueous sodium chloride were added to the mixture. After phaseseparation, the aqueous layer was washed consecutively with aqueous 1Nsodium hydroxide (3 times) and a saturated aqueous solution of sodiumchloride (twice). The washed ethereal solution was dried over magnesiumsulfate and treated with active charcoal. The residue, afterevaporation, was identified as 3-methyl-2-butenyl diazoacetate (5.72 g,85% yield).

Analysis: nmr δ ppm: 1.8 (m, 6H); 4.6 (s, 1H); 4.8 (m, 2H); 5.4 (m, 1H).

3. Preparation of (±)-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane

A solution of 3-methyl-2-butenyl diazoacetate (41.3 mmole, 6.36 g) indioxane (20 ml) was added dropwise to a refluxing solution of cupricacetylacetonate (1.03 mmole, 0.27 g) in dioxane (400 ml) over a periodof 7 hours under an argon atomosphere. After completion of the addition,the reaction mixture was heated under reflux for 1 hour. The crudereaction mixture was distilled to afford(±)-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane (3.85 g, 75% yield); bp110°, 16 mm Hg.

4. Preparation of optically active6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane

A solution of 3-methyl-2-butenyl diazoacetate (980 mg, 6.4 mmoles) indioxane (15 ml) was added dropwise to a solution ofbis[2-butoxy-α-[2-butoxy-5-(1,1-dimethylethyl)phenyl]-5-(1,1-dimethylethyl)-α-[(S)-1-[[2-hydroxyphenyl)methylene]amino]ethyl]benzenemethanolato(2-)]-copper (83 mg, 0.064 mmole) in dioxane (55 ml) at 110°. When theevolution of nitrogen started, the temperature was slowly lowered to52°-3°. The addition took 5.5 hours, and the evolution of almosttheoretical amounts of nitrogen was observed. After the addition wascompleted, the reaction mixture was stirred at 52°-3° for 2 hours,evaporated to dryness, and distilled under vacuum to afford6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane enriched with the (1R,5S)isomer (500 mg). The optical rotation of the product was [α]_(D) ²⁹=-53.5° (CHCl₃).

The product was then treated with base, acidified, then methylated asdescribed by Sevrin, et al., Tetrahedron Letters, 3915 (1976), beforeoxidation to methyl cis-3-formyl-2,2-dimethylcyclopropanecarboxylate.The latter was then converted to a lower alkoxy3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate by theprocedure disclosed in Japan. Kokai 76/122041. The ester was hydrolyzed,and the optical activity of the resultingcis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid was[α]_(D) =+16.7 (CHCl₃), corresponding to an optical yield of about 58%(1R,3R) isomer.

EXAMPLE III Synthesis ofcis-3-(2,2-Dihalovinyl)-2,2-dimethylcyclopropanecarboxylic Acids A.Preparation ofcis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid

To a suspension of zinc powder (0.52 g, 0.008 mole) in 0.6 ml of aceticacid and 3 ml of ether was added dropwise over a period of 15 minutes asolution of4-trichloromethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane (0.487 g,0.002 mole) in 3 ml of ether. The mixture was stirred for two hours atroom temperature, 30 ml of ether and 5 ml of water were added, and themixture was then filtered through Celite filter aid. The organic layerwas separated, washed twice with saturated aqueous sodium chloride,dried over magnesium sulfate, and the ether was evaporated to givecrystalline cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylicacid (0.405 g, 97% yield).

Analysis: nmr δ ppm (CDCl₃): 1.18(s, 6H); 1.92(m, 2H); 6.15(d, 1H);13.27(bs, 1H).

The presence in the nmr spectrum of the single doublet at 6.15 ppmindicates that only the cis isomer is present.

B. Preparation ofcis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid

To a chilled suspension of zinc powder (0.494 g, 0.0076 mole) in 0.57 mlof acetic acid and 3 ml of ether was added dropwise over a period of 20minutes a solution of4-tribromomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane (0.72 g,0.0019 mole) in 5 ml of ether. The mixture was stirred at 0° for onehour. After adding 30 ml of ether and 5 ml of water, the mixture wasfiltered through Celite filter aid. The organic layer was separated,washed three times with saturated aqueous sodium chloride, driedmagnesium sulfate, and the ether was removed by evaporation to givecrystalline cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylicacid (0.489 g, 86% yield); mp, 112°-114° after recrystallization fromn-hexane.

Analysis: nmr δ ppm (CDCl₃): 1.27(s, 6H); 1.97(m, 2H); 6.67(d, 1H);11.3(bs, 1H).

The presence in the nmr spectrum of the single doublet at 6.67 ppm showsthat only the cis isomer is present.

If an optically active4-trihalomethyl-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane isemployed, e.g., enriched with the (1R,4R,5S) optical isomer, anoptically activecis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acid, e.g.,enriched with the (1R,3R) isomer, is obtained.

We claim:
 1. A compound of the formula ##STR10## wherein each X is the same or different and is a chlorine or bromine atom, and R₃ is lower alkoxycarbonyl.
 2. A compound of claim 1 wherein X is a chlorine atom.
 3. A compound of claim 1 which is optically active due to enrichment with the 1R,4R,5S or 1S,4S,5R optical isomer.
 4. A compound of claim 1 which is a racemic mixture of the 1R,4R,5S optical isomer and its mirror image. 